Ageing of the uterine endometrium is a critical factor that affects reproductive success, but the mechanisms associated with uterine ageing are unclear. In this study, we conducted a qualitative examination of age-related changes in endometrial tissues and identified candidate genes as markers for uterine ageing. Gene expression patterns were assessed by two RNA-sequencing experiments using uterine tissues from wild type (WT) C57BL/6 mice. Gene expression data obtained by RNA-sequencing were validated by real-time PCR. Genes expressing the pro-inflammatory cytokines Il17rb and chemokines Cxcl12 and Cxcl14 showed differential expression between aged WT mice and a group of mice composed of 5- and 8-week-old WT (young) animals. Protein expression levels of the above-mentioned genes and of IL8, which functions downstream of IL17RB, were analysed by quantitative immunohistochemistry of unaffected human endometrium tissue samples from patients in their 20s and 40s (10 cases each). In the secretory phase samples, 3,3'- diaminobenzidine staining intensities of IL17RB, CXCL12 and CXCL14 for patients in their 40s were significantly higher than that for patients in their 20s, as detected by a Mann-hitney U test. These results suggest that these genes are candidate markers for endometrial ageing and for prediction of age-related infertility, although confirmation of these findings is needed in larger studies involving fertile and infertile women.Cystic fibrosis (CF) transmembrane conductance (CFTR) dysfunction may play a role in CF-related bone disease (CFBD). Ivacaftor is a CFTR potentiator effective in improving pulmonary and nutritional outcomes in patients with the G551D-CFTR mutation. The effects of ivacaftor on bone health are unknown.
To determine the impact of ivacaftor on bone density and microarchitecture in children and adults with CF.
Prospective observational multiple cohort study.
Outpatient clinical research center within a tertiary academic medical center.
Three cohorts of age-, race-, and gender-matched subjects were enrolled 26 subjects (15 adults and 11 children) with CF and the G551D-CFTR mutation who were planning to start or had started treatment with ivacaftor within 3 months (Ivacaftor cohort), 26 subjects with CF were not treated with ivacaftor (CF Control cohort), and 26 healthy volunteers.
All treatments, including Ivacaftor, were managed by the subjects' pulmonologists.
Bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT), areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and bone turnover markers at baseline, 1, and 2 years.
Cortical volume, area, and porosity at the radius and tibia increased significantly in adults in the Ivacaftor cohort. No significant differences were observed in changes in aBMD, trabecular microarchitecture, or estimated bone strength in adults or in any outcome measures in children.
Treatment with ivacaftor was associated with increases in cortical microarchitecture in adults with CF. Further studies are needed to understand the implications of these findings.
Treatment with ivacaftor was associated with increases in cortical microarchitecture in adults with CF. Further studies are needed to understand the implications of these findings.Transposable elements (TEs) and their reverse complementary sequence pairs (RCPs) are enriched around loci that produce circular RNAs (circRNAs) in plants. However, the function of these TE-RCP pairs in modulating circRNA expression remains elusive. Here, we identified 4609 circRNAs in poplar (Populus tomentosa) and showed that miniature inverted repeat transposable elements (MITEs)-RCPs were enriched in circRNA flanking regions. Moreover, we used expression quantitative trait nucleotide (eQTN) mapping to decipher the cis-regulatory role of MITEs. eQTN results showed that 14 single-nucleotide polymorphisms (SNPs) were significantly associated with Circ_0000408 and Circ_0003418 levels and the lead associated SNPs were located in MITE-RCP regions, indicating that MITE-RCP sequence variations affect exon circularization. Overexpression and knockdown analysis showed that Circ_0003418 positively modulated its parental gene, which encodes the RING-type E3 ligase XBAT32, and specifically increased the expression of the PtoXBAT32.5 transcript variant, which lacks the E3 ubiquitin ligase domain. Under heat stress, PtoXBAT32.5 expression was induced with up-regulation of Circ_0003418, resulting in increased production of ethylene and peroxidation of membrane lipids. Our findings thus reveal the cis-regulatory mechanism by which a MITE-RCP pair affects circRNA abundance in poplar and indicate that Circ_0003418 is a negative regulator of poplar heat tolerance via the ubiquitin-mediated protein modification pathway.Integrative genomic analysis is a powerful tool used to study the biological mechanisms underlying a complex disease or trait across multiplatform high-dimensional data, such as DNA methylation, copy number variation and gene expression. https://www.selleckchem.com/products/gc7-sulfate.html It is common to perform large-scale genome-wide association analysis of an outcome for each data type separately and combine the results ad hoc, leading to loss of statistical power and uncontrolled overall false discovery rate (FDR).
We propose a multivariate mixture model (IMIX) framework that integrates multiple types of genomic data and allows modeling of inter-data-type correlations. We investigated the across-data-type FDR control in IMIX and demonstrated lower misclassification rates at controlled overall FDR than established individual data type analysis strategies, such as the Benjamini-Hochberg FDR control, the q-value and the local FDR control by extensive simulations. IMIX features statistically principled model selection, FDR control and computational efficiency. Applications to The Cancer Genome Atlas data provided novel multi-omics insights into the genes and mechanisms associated with the luminal and basal subtypes of bladder cancer and the prognosis of pancreatic cancer.
We have implemented our method in R package 'IMIX' available at https//github.com/ziqiaow/IMIX, as well as CRAN soon.
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.